Studies of selenium and arsenic mutual protection in human HepG2 cells
Abstract
Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic. Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno-bis(S-glutathionyl) arsinium ion [(GS)2AsSe]-. Consistent with this, human selenium deficiency in arsenic-endemic regions is associated with arsenic-induced disease, leading to the initiation of human selenium supplementation trials. In contrast to the protective effect observed in vivo, in vitro studies have suggested that selenite increases arsenite cellular retention and toxicity. This difference might be explained by the rapid conversion of selenite to selenide in vivo. In the current study, selenite did not protect the human hepatoma (HepG2) cell line against the toxicity of arsenite at equimolar concentrations, however selenide increased the IC50 by 2.3-fold. Cytotoxicity assays of arsenite + selenite and arsenite + selenide at different molar ratios revealed higher overall mutual antagonism of arsenite + selenide toxicity than arsenite + selenite. Despite this protective effect, in comparison to 75Se-selenite, HepG2 cells in suspension were at least 3-fold more efficient at accumulating selenium from reduced 75Se-selenide, and its accumulation was further increased by arsenite. X-ray fluorescence imaging of HepG2 cells also showed that arsenic accumulation, in the presencemore »
- Authors:
-
- Univ. of Alberta, Edmonton, AB (Canada)
- Univ. of Saskatchewan, Saskatoon, SK (Canada)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- Canadian Institutes of Health Research (CIHR); Univ. of Saskatchewan, Saskatoon, SK (Canada); Natural Sciences and Engineering Research Council of Canada (NSERC); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1668071
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Chemico-Biological Interactions
- Additional Journal Information:
- Journal Volume: 327; Journal ID: ISSN 0009-2797
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; Arsenite; Arsenite toxicity; Human cells imaging; Selenium Accumulation; X-ray Fluorescence Microscopy
Citation Formats
Kaur, Gurnit, Ponomarenko, Olena, Zhou, Janet R., Swanlund, Diane P., Summers, Kelly L., Dolgova, Natalia V., Antipova, Olga, Pickering, Ingrid J., George, Graham N., and Leslie, Elaine M. Studies of selenium and arsenic mutual protection in human HepG2 cells. United States: N. p., 2020.
Web. doi:10.1016/j.cbi.2020.109162.
Kaur, Gurnit, Ponomarenko, Olena, Zhou, Janet R., Swanlund, Diane P., Summers, Kelly L., Dolgova, Natalia V., Antipova, Olga, Pickering, Ingrid J., George, Graham N., & Leslie, Elaine M. Studies of selenium and arsenic mutual protection in human HepG2 cells. United States. https://doi.org/10.1016/j.cbi.2020.109162
Kaur, Gurnit, Ponomarenko, Olena, Zhou, Janet R., Swanlund, Diane P., Summers, Kelly L., Dolgova, Natalia V., Antipova, Olga, Pickering, Ingrid J., George, Graham N., and Leslie, Elaine M. Sun .
"Studies of selenium and arsenic mutual protection in human HepG2 cells". United States. https://doi.org/10.1016/j.cbi.2020.109162. https://www.osti.gov/servlets/purl/1668071.
@article{osti_1668071,
title = {Studies of selenium and arsenic mutual protection in human HepG2 cells},
author = {Kaur, Gurnit and Ponomarenko, Olena and Zhou, Janet R. and Swanlund, Diane P. and Summers, Kelly L. and Dolgova, Natalia V. and Antipova, Olga and Pickering, Ingrid J. and George, Graham N. and Leslie, Elaine M.},
abstractNote = {Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic. Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno-bis(S-glutathionyl) arsinium ion [(GS)2AsSe]-. Consistent with this, human selenium deficiency in arsenic-endemic regions is associated with arsenic-induced disease, leading to the initiation of human selenium supplementation trials. In contrast to the protective effect observed in vivo, in vitro studies have suggested that selenite increases arsenite cellular retention and toxicity. This difference might be explained by the rapid conversion of selenite to selenide in vivo. In the current study, selenite did not protect the human hepatoma (HepG2) cell line against the toxicity of arsenite at equimolar concentrations, however selenide increased the IC50 by 2.3-fold. Cytotoxicity assays of arsenite + selenite and arsenite + selenide at different molar ratios revealed higher overall mutual antagonism of arsenite + selenide toxicity than arsenite + selenite. Despite this protective effect, in comparison to 75Se-selenite, HepG2 cells in suspension were at least 3-fold more efficient at accumulating selenium from reduced 75Se-selenide, and its accumulation was further increased by arsenite. X-ray fluorescence imaging of HepG2 cells also showed that arsenic accumulation, in the presence of selenide, was higher than in the presence of selenite. These results are consistent with a greater intracellular availability of selenide relative to selenite for protection against arsenite, and the formation and retention of a less toxic product, possibly [(GS)2AsSe]-.},
doi = {10.1016/j.cbi.2020.109162},
journal = {Chemico-Biological Interactions},
number = ,
volume = 327,
place = {United States},
year = {Sun Jun 07 00:00:00 EDT 2020},
month = {Sun Jun 07 00:00:00 EDT 2020}
}
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